Phosphate-reducing Drugs can Help Prevent Heart Disease in Kidney Patients

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According to researchers at Washington University School of Medicine in St. Louis, drugs that reduce phosphate levels can help protect chronic kidney disease (CKD) patients from cardiovascular disease.

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An estimated 19 million Americans living with CKD face a high risk of death from cardiovascular disease. Recent studies have shown that a main source of this cardiovascular risk is CKD patients' high levels of blood phosphate.

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"One of the kidney's functions is to help maintain a constant balance of phosphate in the bloodstream," says senior author Keith A. Hruska, M.D., director of the Division of Pediatric Nephrology and professor of pediatrics, of medicine and of cell biology and physiology.

"When kidney failure occurs, an excess of serum phosphate develops. It turns out that high phosphate serves as a signal that stimulates cells within blood vessel walls to become bone-forming cells and to deposit calcium crystals. That produces vascular stiffness that is a cause of cardiovascular mortality," Hruska said.

In the study, the research team studied mice with CKD and atherosclerosis - calcified plaques in the arteries. They gave the mice phosphate-binding agents, which prevent phosphate in the diet from entering the bloodstream.

This therapy decreased arterial calcification in the mice. The treatment also diminished the activity of a genetic program that stimulates blood vessel cells to become bone-forming cells.

Skeletal turnover normally allows the bones to assimilate excess phosphate, but in people with CKD, bone turnover is inhibited and excess phosphate stays in the bloodstream. There it can induce the differentiation of blood-vessel-wall cells into bone-forming cells.

Scientists previously identified a growth factor called BMP-7 (bone morphogenic factor-7) that increases skeletal bone formation. In addition to demonstrating the beneficial effect of phosphate-binding drugs, Hruska and colleagues found that giving BMP-7 to CKD mice also reduced phosphate in their bloodstreams and decreased the calcification of blood vessels.

"BMP-7 restores the ability of the skeleton to serve as a reservoir for phosphate, and in the walls of blood vessels it blocks the process of differentiation into bone-forming cells. It's possible that BMP-7 also could someday be developed into a therapy for patients with CKD and have the added advantage of restoring normal skeletal function and protecting the normal physiology of blood vessels," Hruska said.

The study is published in the Journal of the American Society of Nephrology.

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